ABSTRACT E-cigarettes are now the most common tobacco product used by youth in the US. Among the primary reasons youth report for having tried e-cigarettes are low risk perceptions and appealing flavors. Youth have poor knowledge of e-cigarette health risks, which only recently have a required warning label. At the same time, e- cigarettes are advertised in sweet and fruit flavors that increase their appeal to youth. A recent study by our team indicated that these factors also interact ?images of sweet/fruit flavors on e-cigarette advertisements distracted youth from warning labels. To better understand how these factors impact e-cigarette use by youth, there is a critical need for measures linking exposure to e-cigarette advertising and warning labels to future e- cigarette use behavior. Functional magnetic resonance imaging (fMRI) has been used to identify brain activity patterns that predict future health behavior including tobacco use beyond self-report. Multiple fMRI studies indicate that the medial prefrontal cortex (MPFC) response to cigarette warnings predicts future smoking. Other fMRI studies indicate that the nucleus accumbens (NAc) response to advertisements predicts purchasing. This project will use a similar brain-as-predictor approach with fMRI and eye tracking to link neural responses to e-cigarette advertising and warning labels to future e-cigarette use behavior in youth. Adolescents (ages 14-17, N=80) will view e-cigarette advertisements and warning labels in fMRI and complete quarterly follow-up surveys for one year. MPFC and NAc activity will be measured and tested for relationships with future e-cigarette attitudes, intentions and use. Additional fMRI control conditions will allow us to test the specific impact of different categories of warning labels and different e-cigarette flavors, and the interactions between these factors, including their impact on memory for warning labels. Aim 1 will test the hypothesis that greater MPFC activity as adolescents view e-cigarette warning labels will be related to more negative e- cigarette attitudes and intentions and lower use of e-cigarettes in the next year. Exploratory Aim 1.1 will compare MPFC response between warning labels about addictiveness versus chemical constituents. Aim 2 will test the hypothesis that greater NAc activity as adolescents view e-cigarette advertisements will be related to more positive e-cigarette attitudes and intentions and greater use of e-cigarettes in the next year. Exploratory Aim 2.1 will compare the relative value of multiple measures ?fMRI, eye tracking and surveys ?to predict future e-cigarette use in the next year. Aim 3 will replicate and extend our recent study by testing whether images of flavors on e-cigarette advertisements distract adolescents from warning labels. Overall, this project should generate critical evidence on the impact of e-cigarette advertising and warning labels on e-cigarette use behavior in youth, and inform FDA efforts to regulate e-cigarette flavors, labeling and marketing. Important information will also be generated on the relative value of multiple measures to predict future e-cigarette use.